https://scholars.lib.ntu.edu.tw/handle/123456789/552690
標題: | Deacidification by FhlA-dependent hydrogenase is involved in urease activity and urinary stone formation in uropathogenic Proteus mirabilis | 作者: | Lin, Wen-Yuan SHWU-JEN LIAW |
公開日期: | 2020 | 卷: | 10 | 期: | 1 | 來源出版物: | Scientific reports | 摘要: | Proteus mirabilis is an important uropathogen, featured with urinary stone formation. Formate hydrogenlyase (FHL), consisting of formate dehydrogenase H and hydrogenase for converting proton to hydrogen, has been implicated in virulence. In this study, we investigated the role of P. mirabilis FHL hydrogenase and the FHL activator, FhlA. fhlA and hyfG (encoding hydrogenase large subunit) displayed a defect in acid resistance. fhlA and hyfG mutants displayed a delay in medium deacidification compared to wild-type and ureC mutant failed to deacidify the medium. In addition, loss of fhlA or hyfG decreased urease activity in the pH range of 5-8. The reduction of urease activities in fhlA and hyfG mutants subsided gradually over the pH range and disappeared at pH 9. Furthermore, mutation of fhlA or hyfG resulted in a decrease in urinary stone formation in synthetic urine. These indicate fhlA- and hyf-mediated deacidification affected urease activity and stone formation. Finally, fhlA and hyfG mutants exhibited attenuated colonization in mice. Altogether, we found expression of fhlA and hyf confers medium deacidification via facilitating urease activity, thereby urinary stone formation and mouse colonization. The link of acid resistance to urease activity provides a potential strategy for counteracting urinary tract infections by P. mirabilis. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/552690 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-020-76561-w | SDG/關鍵字: | bacterial protein; carbonyl cyanide chlorophenylhydrazone; formate dehydrogenase; hydrogenase; multienzyme complex; urease; anaerobic growth; animal; chemistry; drug effect; female; gene expression regulation; genetics; growth, development and aging; Institute for Cancer Research mouse; metabolism; microbiology; mutation; pathogenicity; pH; promoter region; Proteus infection; Proteus mirabilis; urinary tract infection; urine; urolithiasis; Anaerobiosis; Animals; Bacterial Proteins; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Female; Formate Dehydrogenases; Gene Expression Regulation, Bacterial; Hydrogen-Ion Concentration; Hydrogenase; Mice, Inbred ICR; Multienzyme Complexes; Mutation; Promoter Regions, Genetic; Proteus Infections; Proteus mirabilis; Urease; Urinary Calculi; Urinary Tract Infections; Urine |
顯示於: | 醫學檢驗暨生物技術學系 |
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